The major cause of morbidity and mortality in Cystic Fibrosis (CF) patients is the progressive pulmonary infection caused by Pseudomonas aeruginosa. Although there is no accepted explanation for the susceptibility of CF patients to infection by this particular microorganism, a specific local defect in the immune system is suspected since systematic spread of infection does not occur. Considering the importance of alveolar macrophages for maintaining the sterility of the lower lung, the observation that CF sera couldn't promote the phagocytosis of P. aeruginosa by rabbit alveolar macrophages was particularly relevant. Unfortunately, little information is known concerning human macrophages. With this in mind, this application addresses three specific areas of investigation. First, the identification of human serum components responsible for preventing systemic spread of pseudomonas infections. Second, an examination of the opsonic activity of CF sera for phagocytosis of P. aeruginosa by human phagocytic cells, including polymorphonuclear leukocytes, peripheral monocytes and tissue macrophages. Third, the determination of the ability of Pseudomonas to activate complement. These studies will hopefully provide more information concerning the possibility of a defect in the CF patient's humoral or cellular defense mechanisms which might predispose these patients to infection by Pseudomonas.